The present disclosure generally relates to catalytic methods for producing opioid derivatives. More particularly, the present disclosure relates to the preparation of hydrocodone, hydromorphone, or a derivative thereof, by means of a conversion or an isomerization of codeine, morphine, or a derivative thereof, respectively, using a non-supported, heterogeneous ruthenium metal catalyst.
Hydrocodone and hydromorphone are opiate analgesics having similar qualities to codeine and morphine. Development of new opiate derivatives is desirable to produce new intermediates and potential sources of new analgesics. Conventional methods for producing hydrocodone and hydromorphone typically involve a two step oxidation/reduction route from codeine and morphine, respectively. Unfortunately, these methods can be expensive and inefficient. Attempts to improve efficiency have included the use of catalytic methods. Known catalytic methods include the use of metallic catalysts or complexes, deposited on a support of some kind (e.g., an activated carbon support). However, the preparation of these known catalysts can be difficult. Furthermore, yields are often poor, and isolation of the product is often burdensome. Finally, some catalysts require manufacture and incorporation of expensive supports.
Other known catalytic methods, including the use of finely-divided platinum or palladium in an acidic media, can be environmentally undesirable. Enzymatic methods of conversion have also been attempted. However, like many of the catalysts discussed above, these methods can be costly and difficult to scale up.
Accordingly, a need continues to exist for improved methods for producing various opioids, including hydrocodone, hydromorphone, and derivatives thereof. Desirably, such methods would provide improved yields of the desired reaction product, while enabling the more cost-effective scale up and manufacture of such compounds.